FURTHER EVIDENCE FOR GENETIC ANTICIPATION IN FAMILIAL RHEUMATOID-ARTHRITIS

Objective-To determine whether preliminary evidence supporting feature s of genetic anticipation in familial rheumatoid arthritis (RA) could be replicated in independent and larger samples. Method-Data were obta ined from records of 59 multicase families from the Arthritis and Rheu matism Council (ARC) National Repository in Manchester, 65 multicase f amilies from Cleveland, Ohio, USA, and 253 consecutive patients with R A attending clinics in Nottingham. Results-Mean ages of disease onset in the parents affected with RA were consistently greater than those i n the probands. In the ARC data, the mean age difference in disease on set between the affected mother and proband pairs was 16.0 years (95% confidence interval (CI) 7.2 to 24.8 years, n = 11); in the Cleveland data it was 7.8 years (95% CI 0.9 to 14.7 years, n = 24), and in the N ottingham data it was 10.4 years (95% CI 2.8 to 18.0 years, n = 28). S imilar results were found in the limited number of father-proband pair s. Unlike the findings of earlier work, there was no correlation betwe en proband age at disease onset and age of the parent at conception of the proband. Conclusion-In independent and larger familial RA data se ts, features of genetic anticipation were replicated. Our findings sup port the case for further research at a molecular level into genetic a nticipation in those families with two successive generations affected by RA.